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Published on: February 23, 2014
Microbial and immune determinants of disease severity and death in pediatric pneumonia
Abstract:
Pneumonia is a leading cause of death globally and disproportionately affects children in lower- and middle-income countries. To explore microbial and immune correlates of disease and death, we performed metagenomic sequencing of upper respiratory tract (URT) microbiome in 309 children in Mali with pneumonia and 150 age- and season- and site-matched controls. We show that the URT microbiome matures throughout early life and is influenced by breastfeeding. URT microbiome maturation was disrupted during pneumonia resulting in loss of commensal species and expansion of pathobionts, which was linked to disease severity and death. Analysis of serum antibody levels revealed that low levels of passively acquired antibody from mothers, deficient antibody responses to RSV, and persistent autoantibody to cytokines were associated with pneumonia mortality in an age-dependent manner. These findings underscore the complex nature of pneumonia and identify microbial and immune factors for risk stratification and therapeutic interventions in pediatric pneumonia.
Insights
Pediatric pneumonia is linked to disrupted upper respiratory tract (URT) microbiome maturation and altered immune responses. These factors contribute to disease severity and mortality in children, offering targets for intervention.
Area of Science:
- Microbiology
- Immunology
- Global Health
Background:
- Pneumonia is a major global cause of child mortality, particularly in low- and middle-income countries.
- Understanding the interplay between the microbiome and immune system is crucial for addressing pediatric pneumonia.
Purpose of the Study:
- To investigate the microbial and immune factors associated with pneumonia and mortality in children.
- To explore the role of the upper respiratory tract (URT) microbiome in pediatric pneumonia.
Main Methods:
- Metagenomic sequencing of the URT microbiome in children with pneumonia and healthy controls in Mali.
- Analysis of serum antibody levels, including passively acquired maternal antibodies, anti-RSV antibodies, and autoantibodies to cytokines.
Main Results:
- URT microbiome maturation was disrupted in children with pneumonia, characterized by loss of commensal species and expansion of pathobionts.
- Disrupted microbiome was linked to increased disease severity and mortality.
- Low maternal antibodies, deficient anti-RSV responses, and persistent autoantibodies to cytokines were associated with pneumonia mortality in an age-dependent manner.
Conclusions:
- The URT microbiome and immune factors play complex roles in pediatric pneumonia.
- Microbial and immune profiles can aid in risk stratification for pneumonia.
- Identified factors present potential targets for novel therapeutic interventions.
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